This grant entitled Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) is submitted in response to PAR-12-265 from the NIDDK as an Ancillary study to major ongoing clinical research study to advance areas of scientific interest within the mission of the NIDDK. This proposal will be an ancillary study of te Preterm Epo NeuroProtection Trial (PENUT), a blinded randomized placebo-controlled Phase 3 multi-center trial of Erythropoietin for Neuroprotection in Extremely Low Gestational Age (24-27 weeks) Neonates (ELGANS) funded by NINDS. The NIDDK has supported and secured the use of PENUT clinical data, blood and urine samples from 940 infants randomized to thrice weekly recombinant human erythropoietin (rHuEPO) or placebo. Infants will be followed from birth to 24-26 months corrected age. AKI occurs in approximately 30% of ELGANs. Premature infants are at twice the risk of developing albuminuria, and sustained low GFR leading to end-stage kidney disease than their term counterparts. rHuEPO not only stimulates red blood cell production, but is a promising therapy for tissue protection in the kidney, brain and other organs. This ancillary study provides an unparalleled opportunity to test our central hypothesis that rHuEPO mitigates in- hospital kidney damage in ELGANs, which ultimately decreases CKD at 24-26 months corrected age. As an ancillary study to PENUT, we propose 3 specific aims: Aim 1: We will determine if the degree of kidney damage and other risk factor(s) identified during the neonatal hospitalization predict CKD in ELGANS at 24-26 months corrected age. Aim 2: We will determine if and how rHuEPO improves in-hospital renal outcomes using serum and urine biomarkers of kidney function, injury, repair, inflammation and oxidative stress. Aim 3: We will determine if rHuEPO improves renal outcomes at 24-26 months. This proposal will help us predict which ELGANS develop CKD, determine if and how rHuEPO improves kidney damage, and which biomarkers are modifiable and predictive of hard clinical endpoints. Ultimately, this will improve our ability to define early kidney injury, intervene expeditiously and improve outcomes.